Study Questions:

How do patients with reduced left ventricular ejection fraction (LVEF) and left bundle branch block (LBBB) respond to guideline-directed medical therapy (GDMT)?

Methods:

The study authors made use of the Duke Echocardiography Laboratory Database and the Duke electrocardiography (ECG) database to identify patients with a diagnosis of cardiomyopathy (an LVEF ≤35%, assessed visually by an attending cardiologist with level 3 training in echocardiography), an ECG, and a follow-up echocardiogram in 3-6 months. They excluded patients with severe valve disease, a cardiac device, LV assist device, or heart transplant. QRS morphology was classified as: LBBB, QRS <120 msec (NQRS), or a wide QRS ≥120 msec but not LBBB (WQRS). The primary outcome of this study was change in LVEF over a period of 3-6 months. A secondary outcome assessed rates of LV functional recovery to an LVEF >35%. Clinical outcomes included time to heart failure hospitalization and time to mortality, both measured after follow-up echocardiogram. Analysis of variance (ANOVA) testing compared mean change in LVEF between the three groups, with adjustment for significant comorbidities and GDMT.

Results:

The final study cohort was comprised of 659 patients: 111 LBBB (17%), 59 WQRS (9%), and 489 NQRS (74%). Patients with LBBB were more likely to be older, female, and have cerebrovascular disease. Patients with WQRS were more likely to have had a prior myocardial infarction, be on statin medications, and have an enlarged left atrium. Patients with NQRS tended to be younger, have faster heart rates, and have less baseline heart failure. Adjusted mean increase in LVEF over 3-6 months in the three groups was 2.03 (LBBB), 5.28 (WQRS), and 8.00 (NQRS), respectively (p < 0.0001). Results were similar when adjusted for interim revascularization and myocardial infarction. Comparison of mean LVEF improvement between patients with LBBB on GDMT and those not on GDMT showed virtually no difference (3.50 vs. 3.44%). At follow-up, 23% of patients with LBBB improved their LVEF to >35%, compared to
27% with WQRS, and 43% with NQRS. On the whole, patients with LBBB were more likely to stay the same or worsen their LVEF on follow-up and the least likely to improve their LVEF to >35%. In patients with NQRS, the odds of LV functional recovery past an LVEF >35% were 2.57 (95% confidence interval, 1.59-4.15) times higher than in patients with LBBB (p = 0.001). Patients with WQRS had a nonsignificant 1.28 times greater odds than LBBB patients (p = 0.51). This relationship was essentially unchanged when adjusted for comorbidities. The combined endpoint of heart failure hospitalization or mortality (median follow-up was 4.3 years) was highest for patients with LBBB.

Conclusions:

The study authors concluded that LBBB is associated with a smaller degree of LVEF improvement compared to other QRS morphologies, even with GDMT and/or revascularization. They proposed that some patients with LBBB may benefit from cardiac resynchronization therapy (CRT) earlier than guidelines currently recommend.

Perspective:

This is an important study because it suggests that patients with LBBB should be considered for CRT possibly as soon as the diagnosis of LBBB is made. Like all risk factors, the width of QRS complex as a predictor of risk is a continuum. It would be interesting to determine whether, indeed, patients with a QRS width >108 msec portends poor prognosis and whether early intervention with CRT would benefit such patients.